Targeting the activity of T cells by membrane surface redox regulation for cancer theranostics PMID: 36536041

ADC Targets in Oncology

2026-04-10

Targeting the activity of T cells by membrane surface redox regulation for cancer theranostics

Nat Nanotechnol. 2022 Dec 19. doi: 10.1038/s41565-022-01261-7.

Changrong Shi ^# ¹ , Qianyu Zhang ^# ¹ , Yuying Yao ² , Fantian Zeng ¹ , Chao Du ¹ , Sureya Nijiati ¹ , Xuejun Wen ¹ , Xinyi Zhang ¹ , Hongzhang Yang ¹ , Haoting Chen ² , Zhide Guo ¹ , Xianzhong Zhang ¹ , Jinhao Gao ³ , Weisheng Guo ⁴ , Xiaoyuan Chen ⁵ ⁶ ⁷ ⁸ , Zijian Zhou ⁹

Affiliations

1. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, Department of Laboratory Medicine, School of Public Health, Xiamen University, Xiamen, China.
2. Department of Minimally Invasive Interventional Radiology, State Key Laboratory of Respiratory Disease, School of Biomedical Engineering & the Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
3. State Key Laboratory of Physical Chemistry of Solid Surfaces & The Key Laboratory for Chemical Biology of Fujian Province, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, China.
4. Department of Minimally Invasive Interventional Radiology, State Key Laboratory of Respiratory Disease, School of Biomedical Engineering & the Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China. [email protected].
5. Departments of Diagnostic Radiology, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore, Singapore. [email protected].
6. Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. [email protected].
7. Nanomedicine Translational Research Program, NUS Center for Nanomedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. [email protected].
8. Institute of Molecular and Cell Biology, Agency for Science, Technology, and Research (A*STAR), Singapore, Singapore. [email protected].
9. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, Department of Laboratory Medicine, School of Public Health, Xiamen University, Xiamen, China. [email protected].
# Contributed equally.

Abstract

T cells play a determining role in the immunomodulation and prognostic evaluation of Cancer treatments relying on immune activation. While specific biomarkers determine the population and distribution of T cells in tumours, the in situ activity of T cells is less studied. Here we designed T-cell-targeting fusogenic liposomes to regulate and quantify the activity of T cells by exploiting their surface redox status as a chemical target. The T-cell-targeting fusogenic liposomes equipped with 2,2,6,6-tetramethylpiperidine (TEMP) groups neutralize Reactive Oxygen Species protecting T cells from oxidation-induced loss of activity. Meanwhile, the production of paramagnetic 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) radicals allows magnetic resonance imaging quantification of the T cell activity. In multiple mouse models, the T-cell-targeting fusogenic liposomes led to efficient tumour inhibition and to early prediction of radiotherapy outcomes. This study uses a chemical targeting strategy to measure the in situ activity of T cells for Cancer theranostics and may provide further understanding on engineering T cells for Cancer treatment.